Calcium channels are multi-subunit protein complexes that span the plasma membrane and arc involved in the movement of calcium ions into the cell. Voltage-dependent calcium channels, the most common type of calcium channels, are classified as L-, T-, N-, or P-type channels, based on conductance levels, sensitivity to agonists and antagonists, and holding potential (K. Dunlap et al., Trends Neurosci. 18:89-98 (1995)). Calcium channels contain two large subunits, .alpha.1 and .alpha.2, having molecular weights between about 130 and about 200 kDa, and one to three smaller subunits, such as .beta., and/or .gamma. subunits, each having a molecular weight that is usually less than about 60 kDa. At least one of the large subunits is glycosylated, and a smaller subunit may be glycosylated as well. Subunit .alpha.1 is approximately 200 to about 230 kDa, based on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). This subunit forms the pore through which calcium enters cells. Subunit .alpha.2 is approximately 160 to 190 kDa under non-reducing conditions on SDS-PAGE. The .beta. subunit is about 52 to 65 kDa (SDS-PAGE); it is insensitive to reducing conditions. The .gamma. subunit, which is not observed in nervous tissue or in other certain preparations, is a glycoprotein of approximately 30 to 33 kDa (SDS-PAGE).
Investigation of particular calcium channel subtypes is rendered difficult by the presence of a mixture of different tissue-specific types of calcium channels in cells. Study of particular subtypes is essential, however, because of the importance of intracellular calcium levels in contributing to vital cellular processes including neurotransmitter release, muscle contraction, pacemaker activity, and secretion of hormones and other substances. A need remains for identifying and studying individual calcium channel subtypes.